ABSTRACT OF RESEARCH PLAN. The specific aims of this research project are to purify and characterize biochemically the folate binding protein(s) from human tissues, determine its function(s) in cell metabolism, and determine if perturbation of this protein is associated with clinical disorders of the blood forming tissue. The folate binding proteins will be purified by affinity chromatogrphy from the spleen from patients with myeloproliferative diseases. The purifies protein will be subjected to biochemical analysis to determine its amino acid and carbohydrate components and characterization of its structural-functional properties. The folate binding protein will be quantified by radioimmunoassay and immunofluorescent cytology in hemaotpoietic cells in various phases of cell growth and maturation to determine if there is a relationship between this protein and cell replication. Studies will also be conducted to determine whether the folate binding protein can modulate folate-dependent enzymatic reactions by sequestering the folate cofactors and whether these proteins can transport folate into nuclei and induce the synthesis of enzymes required in folate metabolism. Finally, the folate binding protein will be analyzed in hematopoietic cells from patients with megaloblastic anemia, refractory anemias, toxic disorders affecting bone marrow cells (particularly alcohol) and in proliferative disease of erythroid and granulocytic precursor cells. The long-term objectives of this work are to establish whether this protein has a specific function which is critical to cell replication and viability and whether a disturbance of its function results in clinical disease.